Motor disorder Flashcards
the motor cortex is classified into 2 main pathways what are they?
- lateral pathway
2. ventralmedial pathway
describe the lateral pathway
what are the main tracts? (from where to where)
what role does it play in movement
- cortico-spinal tract (from cortex to SC)
- rubro-spinal tract (from red nucleues in midbrain to SC, more important in children as smaller pathway)
Voluntary skilled movement by Direct cortical control
describe the ventro-medial motor pathway
what are the main tracts? (from which part of brain to where)
what role does it play in movement
- reticulospinal tract (from reticular nuclei in cerebellum in midbrain to SC) = postural control and reflex movement
- tectospinal tract (from superior colliculus in midbrain to SC, superior colliculus is higher up than medulla) = visual
- vestibulospinal tract (from vestibular nuclei in medulla in midbrain to SC) = auditory and balance
what is the overall effect of the lateral and ventro-medial pathways?
Coordinates the visual and auditory input w movement, direct you to turn around when you heard a sound/ react when see things
which two compotents are involved in the striatum part of the brain in the basal ganglia
why is it called striatum?
putamen and caudate nucleus
take away the top you see striation like tiger pattern
What is the basal ganglia consist of?
Striatum (putamen and caudate nucleus), external globus pallidus Gpe, internal globus pallidus Gpi, subthalamic nucleus STN, substantia nigra SN (zona compacta SNc and zona reticulata SNr
NOT thalamus!! (only receive output from basal ganglia)
why is substantia nigra important in parkinsons?
SN modifies the action/output from basal ganglia, this ability is lost in parkinsons
why is thalamus important in motor pathway?
receive output from basal ganglia and provide feedback pathway to the cortex, modulate the output from basal ganglia
Describe the brain region involved from deivision making, volition, planning to execution of an action
Cortex – prefrontal (making the decision), sensory (ventromedial pathway receive input), prefrontal cortex send signal to basal ganglia to thalamus (receive output and feedback to motor cortex, modulate CST output), basal ganglia send signal to red nucleus, reticular nuclei and superior colliculus and vestibular nuclei to give an action
Describe the stages of cortico-cerebellar connections. What is its purpose?
From sensory cortex down to cortico-ponto-cerebellar tract to the pontine nuclei then to the cerebellum cortex. The deep cerebellum nuclei send signal up to ventral thalamus via cerebellar feedback pathway- cerebellar-cortico tract. From thalamus to motor cortex. Down cortico-spinal tract to SC. The purpose includes motor learning and movement adjustment. Eg play a piano
What is Tourette’s syndrome? What went wrong in the basal ganglia? How can it be treated?
Rapid movement with stereotyped/ inappropriate sounds or speech. Inreased activity in NS pathway (high level of DA, increased output) treated w D2 rec-antagnoist (antipsychotic w s/e)
What does OCD stands for? Is it a disorder caused by abnormal basal ganglia? What treatment can be given?
Obsessive-compulsive disorder, it is caused by lesions in caudate/putamen in striatum which gives repetitive motor repsonse. Treated with SSRI (only treat change in mood not the cause)
prevelence of parkinsons
0.1% of population, disease of the elderly
What are the parkinsons symptoms?
1 Bradykinesia – slow of movement 2 Akinesia – absence/reduction of move, restlessness 3 Rigidity 4 Tremor – pill rolling finger movement 5 Poor balance 6 Problem with initiating gait 7 Speech problems – if speech muslce affected Progressive, Can cause depression
Describe the pathology of parkinsons in term of genetic
Genetic mutations of alpha-synuclein proteins which causes protein aggregation – forms insoluble lewy bodies –intracellularly inclusion of lewy bodies. Mutant parkin or ligase meaning ligase can no longer break down proteins, so prevents proteolysis. Oxidative stress from mito dysfunction. Overall causes (DA) cell death in (SNc of the) NS pathway
what is the knock-on consequences of SNc degeneration in parkinson?
Loss of DA neurones - imbalance in direct and indirect pathways increases activation of Gpi via indirect Decreases inhibition via direct (Gpi) Increases inhibition of thalamus Switches off thalamo-cortical pathways Loss of cortico-spinal output Decreased movement, rigidity etc
Treatement for parkinsons (outline 1st line)
brand name drugs?
1st line- oral L-DOPA (tyrosine hydroxylase is rate limiting, saturable conversion, so give L-DOPA can increase the DA level. It is converted to DA by DOPA-decarboxylase)
Combined use with peripheral decarboxylase inhibitors e.g. carbidopa, benserazide to reduce s/e
- madopar : cobenedopa (s/e constipation)
- sinemet : cocareldopa (Ldopa+ carbidopa)
- duoDopa : cont duodenal infusion of sinemet
What are the downsides of L-DOPA
1 time limited. No long term benefit because parkinson is a progressive degeneration of neurone, run out of DA neuron to act on
2 Dsykinesias – like huntington
3 On-off syndrome
4 Nausea (DA in emetic centre)
5 Hypotension (DA on alpha1 rec, vasodilation)
6 Anorexia
7 Psychosis (DA on D2 rec mesolimbic pathway, increase +ve sym) pronography
what are the other trt options for parkinsons?
DA receptor agonists: bromocriptine, pramipexole, apomorphine, rotigotine (inc patch) (s/e hallucination, sleepiness, impulsive)
retard degradation: COMT inhibitors - entacapone, MAO inhibitors - selegiline, rasagaline (s/e lesser hallucination)
DA release (increase): Amantadine – less effective than ldopa (less evidence)
Combination therapy with L-DOPA for max clinical benefit
prevelence of huntington and age onset
Low incidence 0.01%- very low!
Appears between 30 and 50yrs
relationship of motor and cognitive sym of huntingtons
Cognitive decline before motor
sym of huntingtons
Chorea - involuntary jerking Grimacing (make faces) Balance and gait (walking) problems Cognitive decline, memory loss, depression Swallowing and speech Death 10-20 years following diagnosis
What is the pathology of huntingtons?
Cell dealth in caudate/putamen–>impaired SN, striato-pallidal pathway but PRESERVED NS pathway (SNc is ok)
Hutington protein is normal in human body, but mutated huntington protein aggreagates and mirgrate from cytosol to nucleus and cause apoptosis. Also expanded repeats of codon for glutamine
describe the Knock-on consequences of striatal degeneration
Loss of caudate neurones decreased inhibition of GPe increased inhibition of STN Decreased excitation of GPi/SNc Decreased inhibition of thalamus Increased thalamo-cortical activity Increase in cortico-spinal output Hyperkinesia, facial tics etc
